Alzheimer's disease, which is characterized by progressive loss of memory and cognitive function affects 15 million people worldwide, with the prevalence increasing from 3% at age 65 years to 47 percent after the age of 85 years. The average cost of an AD patient's care from diagnosis to death is $174,000, and it is estimated that AD costs the US $95 billion annually in lost productivity, medical care and personal caretaking. There is no curative therapy for this condition. A central hypothesis for the apoptotic death of neurons in AD involves the neurotoxic function of the products of enzymatic cleavage of amyloid precursor protein (APP). We have already demonstrated that a truncated form of the product of beta-secretase activity on APP, trAPP, can induce neuronal apoptosis. We will further characterize the ability of a family of full-length and truncated forms of sAPP(beta) to induce neuronal apoptosis in AD. This will then form the basis of a program to develop dendritic cell based immunotherapy for AD. PROPOSED COMMERCIAL APPLICATION: AD affects 15 million people worldwide and costs $95 billion annually in care and lost productivity. Identification and production of the apoptosis inducing sAPP(beta) peptide(s) will allow the development of novel immunotherapeutic treatment.